The p-defensins are natural antibiotics expressed by oral epithelia and secreted in saliva. These peptides have broad specificity against bacteria, fungi, and some viruses. They are thought to have a role in oral health as natural antibiotics. (5-defensin levels vary between individuals, and those with defects in the expression or function of Pdefensins may be susceptible to recurrent infection. Dental caries is an infection; individuals and populations have differing susceptibility to caries. Caries risk is thought to be due to bacterial exposure, diet, and cultural behaviors, but may also be related to biological factors that are due to genetic differences. p-Defensins may have multiple potential effects on bacteria that colonize the tooth surface, altering biofilm formation, acting directly on bacterial survival, and acting synergistically with other antimicrobial factors. Previous observations on activity, localization and secretion of P-defensins lead to the hypothesis that the p-defensin, hBD-1, may be associated with risk for dental caries and that low expression levels, or genetic changes in the function or expression of the peptide, could place an individual at risk for caries. This laboratory has established immunoassays for hBD-1 expression in gingiva and saliva, determined multiple single nucleotide polymorphisms (SNPs) in the^DEFBl gene encoding hBD-1, and examined SNP frequency in different ethnic groups. For this study we have identified a population of Hispanic children in Toppenish, WA, a rural agricultural community near Heritage College, a minority institution that serves Hispanic and Native American students. Appropriately 35% of these children have had 4 or more caries, while nearly 40% have had no caries. Using these preliminary findings and new SNP assays, the goal of this proposal is to conduct a case-control study to explore the relationship between hBD-1 peptide and caries risk in a group of Hispanic children by determining (1) Do caries-prone children have low levels of hBD-1? and (2) Do caries-prone populations have SNPs in hBD-1 that are associated with caries risk? In addition, we will determine association of individual SNPs with salivary hBD-1 levels. Our project is an exploratory study designed to foster development of genetic tools as risk factors for caries susceptibility. The risk of caries is highly related to under-served populations and minority ethnic groups, therefore, any new approaches may help in directing attention to the problem and care to those in need.